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Development of Novel Risk Assessment and Screening Approaches for Microcystin Congeners in Freshwater Harmful Algae BloomsEPA Grant Number: FP917148
Title: Development of Novel Risk Assessment and Screening Approaches for Microcystin Congeners in Freshwater Harmful Algae Blooms
Investigators: Reogner, Amber Ford
Institution: University of California - Davis
EPA Project Officer: Cobbs-Green, Gladys M.
Project Period: August 15, 2010 through August 14, 2013
Project Amount: $111,000
RFA: STAR Graduate Fellowships (2010) RFA Text | Recipients Lists
Research Category: Academic Fellowships , Fellowship - Pesticides and Toxic Substances
With rising global temperatures and surface nutrient runoff, harmful toxin-producing cyanobacterial blooms in freshwaters worldwide only stand to increase. The persistent microcystins, the most commonly identified family of toxins present in these freshwater blooms, continue to pose a public health threat in surface waters utilized for drinking and recreation worldwide. Yet huge gaps in risk assessment of the over 80 structural variants remain, along with many unknowns regarding mechanism of toxicity in the diverse species affected by the potent liver toxin. This project will evaluate comparative congener hepatotoxicity, probe species differences in hepatocellular uptake of the toxins to better understand mechanism of toxicity, and aim to improve available detection techniques in water and biological matrices. In addition to enabling screening for potentially effective antidotes in various species, the work will potentially improve evaluation of risk from drinking water and seafood in chronically exposed human populations through improved detection techniques.
Microcystins (MCs) are potent liver toxins produced in freshwater blooms worldwide. MCs affect diverse species from fish to cows to humans in environmental waters and present a public health threat, as they persist in boiled drinking water. Over 80 structural variants exist, yet risk assessment relies on one variant. This project will evaluate comparative toxicity and species differences, screen for antidotes, and more thoroughly evaluate extent of exposure in human populations.
The first stage of the research will compare congener hepatotoxicity in vitro relative to the most current marker of toxicity, protein phosphatase inhibition, and probe whether alternative markers offer a better predictor of hepatoxicity. Primary mammalian and piscine cells will be utilized to evaluate species differences in uptake and susceptibility to toxicity. In addition, the novel approach of aggregate culture will be utilized to facilitate more in vivo-like and sustained function of both primary hepatocytes and immortalized cell lines with potential application to direct toxicity screening of water samples. Finally, international work will include the development and application of a low-cost, easy-to-use, monoclonal ELISA to evaluate the extent of exposure via drinking water and seafood sources globally.
Because of previous case reports of animal intoxications linked to other congeners, it is expected that microcystin-LR will not be the congener with greatest hepatocellular toxicity and that protein phosphatase inhibition will not be a good predictor of relative congener hepatocellular toxicity. In addition, it is expected that hepatocellular uptake of the toxins will play a substantial role in species differences and be a good predictor of toxicity in vitro. Not only will these results provide guidance for monitoring and improved risk assessment, but also lend insight into mechanisms of toxicity and potential intervention strategies for both humans and veterinary species. The development of a low-cost, easy-to-use, monoclonal ELISA will facilitate detection in both drinking water and biological matrices in low-income areas of the world for improved detection and evaluation of chronic exposure.
Potential to Further Environmental/Human Health Protection:
The work will provide a more thorough evaluation of comparative congener toxicity in addition to species differences in toxicity that can directly be utilized to make improved monitoring and risk assessment suggestions for communities potentially exposed to the toxins in freshwaters worldwide. In the case of acute scenarios, it may lead to an antidote or alternative intervention strategy, while a more rugged, low-cost ELISA will enable a more thorough evaluation of chronic exposures through drinking water or food sources in developing nations.